TY - JOUR
T1 - Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients
AU - Michalovich, David
AU - Rodriguez-Perez, Noelia
AU - Smolinska, Sylwia
AU - Pirozynski, Michal
AU - Mayhew, David
AU - Uddin, Sorif
AU - Van Horn, Stephanie
AU - Sokolowska, Milena
AU - Altunbulakli, Can
AU - Eljaszewicz, Andrzej
AU - Pugin, Benoit
AU - Barcik, Weronika
AU - Kurnik-Lucka, Magdalena
AU - Saunders, Ken A
AU - Simpson, Karen D
AU - Schmid-Grendelmeier, Peter
AU - Ferstl, Ruth
AU - Frei, Remo
AU - Sievi, Noriane
AU - Kohler, Malcolm
AU - Gajdanowicz, Pawel
AU - Graversen, Katrine Bækby
AU - Bøgh, Katrine Lindholm
AU - Jutel, Marek
AU - Brown, James R
AU - Akdis, Cezmi A
AU - Hessel, Edith M
AU - O'Mahony, Liam
PY - 2019
Y1 - 2019
N2 - In order to improve targeted therapeutic approaches for asthma patients, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as obese asthmatics or severe asthmatics, are required. Here we report immunological and microbiome alterations in obese asthmatics (n = 50, mean age = 45), non-obese asthmatics (n = 53, mean age = 40), obese non-asthmatics (n = 51, mean age = 44) and their healthy counterparts (n = 48, mean age = 39). Obesity is associated with elevated proinflammatory signatures, which are enhanced in the presence of asthma. Similarly, obesity or asthma induced changes in the composition of the microbiota, while an additive effect is observed in obese asthma patients. Asthma disease severity is negatively correlated with fecal Akkermansia muciniphila levels. Administration of A. muciniphila to murine models significantly reduces airway hyper-reactivity and airway inflammation. Changes in immunological processes and microbiota composition are accentuated in obese asthma patients due to the additive effects of both disease states, while A. muciniphila may play a non-redundant role in patients with a severe asthma phenotype.
AB - In order to improve targeted therapeutic approaches for asthma patients, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as obese asthmatics or severe asthmatics, are required. Here we report immunological and microbiome alterations in obese asthmatics (n = 50, mean age = 45), non-obese asthmatics (n = 53, mean age = 40), obese non-asthmatics (n = 51, mean age = 44) and their healthy counterparts (n = 48, mean age = 39). Obesity is associated with elevated proinflammatory signatures, which are enhanced in the presence of asthma. Similarly, obesity or asthma induced changes in the composition of the microbiota, while an additive effect is observed in obese asthma patients. Asthma disease severity is negatively correlated with fecal Akkermansia muciniphila levels. Administration of A. muciniphila to murine models significantly reduces airway hyper-reactivity and airway inflammation. Changes in immunological processes and microbiota composition are accentuated in obese asthma patients due to the additive effects of both disease states, while A. muciniphila may play a non-redundant role in patients with a severe asthma phenotype.
U2 - 10.1038/s41467-019-13751-9
DO - 10.1038/s41467-019-13751-9
M3 - Journal article
C2 - 31836714
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 5711
ER -